This grant seeks to explore the metabolic response to infection and the consequences of nutrient intake on parameters of nitrogen metabolism. Loss of lean tissue is the usual result of injury, infection, or operative trauma along with increased urinary excretion of nitrogen, sulphur and potassium. The concept that increased nitrogen loss following injury or infection could result from changes in either protein synthesis or breakdown based on kinetic data has promoted investigation into the nitrogen sparing mechanism of common hypocaloric feedings. The overall response to injury and infection appears to maintain adequate circulating quantitites of metabolic fuels and free amino acids for visceral protein synthesis. Under these conditions, active tissues such as liver and some plasma proteins are spared at the expense of muscle and connective tissue. Various types of hypocaloric nutritional support may either adversely affect or promote this injury response. Investigations under this grant have shown that dietary protein improves protein synthesis and enhances the metabolic response to injury and infection. Carbohydrate, although nitrogen sparing, reduces protein breakdown and may impair the injury response. Other results from our studies have demonstrated that leukocyte endogenous mediator, one of the factors that elicit the injury response, is depressed in malnutrition and restored within one week by nutritional support. The use of isotope tracers for measuring changes in protein dynamics should provide a more rational approach to the nutritional support of the patient.